What is the Process of Making Medicine?

Pharmaceutical manufacturing is the process of producing medications on a large scale as part of the pharmaceutical industry. Milling, granulation, coating, tablet pressing, and other unit operations are examples of pharmaceutical manufacturing processes.

Scale-up Considerations

• Cooling - While dry ice may be used in a laboratory to increase reaction selectivity, this technique becomes more complicated on an industrial scale. The cost of cooling a traditional reactor to this temperature is high, and the viscosity of the chemicals often increases as temperature falls (making mixing more difficult). This raises the costs associated with stirring more vigorously and substituting components more often, resulting in a non-homogeneous reaction. Finally, lower temperatures may promote the crusting of reagents, intermediates, and byproducts to the reaction vessel over time, resulting in decreased product purity.
• Solvent Extractions - On a large scale, the choice to add organic solvent to an aqueous solvent (or vice versa) becomes essential. Emulsions can form depending on the solvents used, and the time required for layers to separate can be extended if the mixing between the solvents is not optimal. Stoichiometry must be examined when adding an organic solvent to aqueous, since excess water may hydrolyze organic molecules even in mildly acidic or basic conditions. The location of the chemical plant, in a larger sense, may impact the temperature of the reaction vessel. Even subtle temperature differences can result in significantly differing extraction quantities among plants in various regions.
• Stoichiometry - Distinct reagent stoichiometric ratios may produce different product ratios. On an industrial scale, adding a considerable amount of reagent A to reagent B can take some time. During this period, the additional reagent A is exposed to a much greater stoichiometric amount of reagent B until it is entirely added. Because of this imbalance, reagent A may react early, and subsequent products may react with an enormous excess of reagent B.

Unit Operations

• Powder Feeding in Continuous Manufacturing - Continuous production involves the continuous supply of raw materials and energy into the system plus the extraction of output products consistently. The uniformity of the material flow rate is critical to the process's success. Because feeding is often the first unit operation in powder-based continuous processes, it is critical to feed powders consistently (and properly) into the process line's subsequent unit activities. Feeders have been designed to give high reliability, accurate feed rate control and minimum disruptions. The correct, consistent distribution of ingredients through well-designed feeders ensures the process's overall stability. Loss-in-weight (LIW) feeders are utilized in pharmaceutical manufacturing. LIW feeders manage material dispensing precisely by weight and are often utilized to eliminate flow rate variability based on infill level and material bulk density. Powder flow parameters, in particular, have a significant impact on feeding performance.

• Milling is often required throughout the medication production process to reduce the average particle size in a drug powder. A few reasons for this include enhanced homogeneity and dosage uniformity, higher bioavailability and increased therapeutic component solubility. In certain cases, repeated powder blending followed by milling is employed to improve the manufacturability of the mixtures.

• Powder Blending - In the pharmaceutical industry, a number of excipients may be mixed with the active pharmaceutical ingredient to generate the final blend necessary to make the solid dosage form. The range of components that can be blended (excipients, API) presents many aspects that must be addressed to achieve the required product quality attributes. These parameters include particle size distribution (including aggregates or lumps of material), particle shape (spheres, rods, cubes, plates, and irregular), the presence of moisture (or other volatile substances), particle surface characteristics (roughness, cohesiveness), and powder flow qualities.

• Hot-Melt Extrusion - Hot-melt extrusion is used in pharmaceutical solid oral dosage manufacture to provide poor solubility and bioavailability medications. Hot-melt extrusion has been found to molecularly distribute poorly soluble medications within a polymer carrier, boosting dissolution rates and bioavailability. Heat, pressure, and agitation are used to mix materials and “extrude” them using a die. Twin-screw high-shear extruders combine materials and break them up; the particles created may then be combined and compressed into pills or capsules.

• Granulation - Wet granulation and dry granulation are the two forms of granulation. Granulation is the inverse of milling; it links microscopic particles together to form larger particles known as granules. Granulation is used for a range of applications. Granulation also prevents "demixing" of components in a combination by forming a granule that preserves all of the components to their required proportions, improves flow characteristics of powders, and increases compaction properties for tablet manufacture.

Documentation

Documenting activities of pharmaceutical manufacturers is a license-to-operate requirement that supports both the quality of the product produced and the satisfaction of regulators who oversee manufacturing operations (and decide whether a manufacturing process can be continued or if it must be terminated and remediated).

Site Master File (SMF)

A Site Master File (SMF) is a document in the pharmaceutical business that provides information on the production and management of industrial processes; a manufacturer creates the paperwork. The SMF contains extensive and accurate GMP information on the production and administration of pharmaceutical manufacturing activities at the defined site, plus any related operations at adjacent and border facilities. If just a fraction of a pharmaceutical procedure is performed on the site, the site master file must list only these operations.

For more information about the pharmaceutical manufacturing process, please visit us at rondaxe.com or call us in New York state at (315) 469-2800.